Mar 3, 1980 - Lewis, B., A. Chait, I. D. P. Wootton, C. M. Oakley,. D. M. Krikler, G. Sigurdsson, A. February, .... G. L. Mills. 1973. The lipids and lipoproteins of ...
Individual Variation in the Effects of Dietary Cholesterol on Plasma Lipoproteins and Cellular Cholesterol Homeostasis in Man STUDIES OF LOW DENSITY LIPOPROTEIN RECEPTOR ACTIVITY AND 3-HYDROXY-3-METHYLGLUTARYL COENZYME A REDUCTASE ACTIVITY IN BLOOD MONONUCLEAR CELLS P. MISTRY, N. E. MILLER, M. LAKER, W. R. HAZZARD, and B. LEWIS, Department of Chemical Pathology and Metabolic Disorders, St. Thomas' Hospital Medical School, London, England
reduction of LDL receptor activity (-74%; P < 0.01), quantified as the rate of degradation of 125I-LDL to noniodide trichloroacetic acid-soluble material. These results provide the first direct evidence for the modulation of LDL receptor activity and HMG CoA reductase activity in a peripheral cell type in response to a dietary perturbation of human lipoprotein metabolism. The percentage increase in LDL cholesterol was negatively correlated with the percentage decrease in HMG CoA reductase activity (r = -0.49, P < 0.01). An additional negative correlation existed between the increment in plasma cholesterol concentration and the capacity of cells to degrade 125I-LDL after derepression by preincubation for 72 h in lipoproteindeficient medium (r = -0.74, P < 0.001). Thus, differences between individuals in the responses of the plasma lipoproteins to dietary cholesterol appear to be related in part to differences in the capacity of increased. These effects on plasma lipoproteins were accom- peripheral cells to catabolize LDL and to downpanied by three changes in freshly isolated blood regulate cholesterol synthesis. mononuclear cells: (a) an increase in cell cholesterol content (mean change, + 17%; P < 0.01); (b) suppresINTRODUCTION sion of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity (-32%; P < 0.001); and (c) Dietary cholesterol is a determinant of the plasma cholesterol concentration in man (1). Considerable This work was presented in part at the 49th Scientific been reported between individuals, have differences Sessions of the American Heart Association, Miami Beach, Florida, November 1976, and at the 25th Colloquium on the however, in the magnitude of the change in plasma Protides of the Biological Fluids, Bruges, Belgium, May 1977. cholesterol induced by a given change in cholesterol Dr. Hazzard was on sabbatical leave from the Department consumption (1-5). Steroid balance studies have of Medicine, University of Washington, Seattle. Address shown that there are also large differences between reprint requests to Dr. Lewis. Received for publication 3 March 1980 and in revised individuals in the extent to which dietary cholesterol is retained within body cholesterol pools (6). form 25 September 1980. A B S T R A C T The effects of dietary cholesterol on plasma lipoproteins and cholesterol homeostasis in blood mononuclear cells have been examined in healthy adults. Addition of 1,500 mg of cholesterol to the daily diet of 37 subjects for 14 d was associated with a wide range of response of plasma total cholesterol concentration (from -6 to +75 mg/dl; mean change, +29 mg!dl; P
